Biomedical subjects

C G Fraga

Publications and source records attributed to C G Fraga.

At least 19 recordsLinked to original sources

PubMed1999

Oxidative stress in testes of rats subjected to chronic iron intoxication and alpha-tocopherol supplementation.

Oxidative stress parameters were evaluated in rat testes after chronic iron intoxication and vitamin E supplementation. Male Wistar rats were fed during 6 weeks with the following diets: C = rat chow; I = C + 25 mg carbonyl-iron/g diet; A = C + 0.2 mg alpha-tocopheryl acetate/g diet; and the combination of I and A (IA). After the treatment, no changes in final body weight, testis weight and protein content were observed. Total iron content in testes from the I group was 33% higher compared to the C group (216 +/- 10 nmol/g of tissue). The content of alpha-tocopherol (alphaT) was 2.5-fold higher in the A and IA groups compared to the C group (12.8 +/- 0.7 nmol/g tissue). The content of ubiquinol-9 (13.0 +/- 1.7 nmol/g tissue) and ubiquinol-10 (3.3 +/- 0.5 nmol/g tissue) was similar among the groups. Superoxide dismutase activity was 13 and 16% lower in the A and IA groups with respect to the C group (12.9 +/- 0.7 U/mg protein). Catalase activity was 26 and 33% lower in the I and IA groups than in the C (0.19 +/- 0.01 pmol/mg protein) and A (0.21 +/- 0.01 pmol/mg protein) groups, respectively. Glutathione peroxidase was 24 and 23% higher in the IA group than in the C (11.4 +/- 0.3 mU/mg protein) and I (11.5 +/- 1.0 mU/mg protein) groups, respectively. The testes content of 2-thiobarbituric acid-reactive substances (TBARS) and protein-associated carbonyl groups were 37 and 16% higher, respectively, in the I group than in the C group. These increased in TBARS and carbonyls, were not observed in the IA group. No diet-associated changes were observed in the steady state levels of 8-oxo-2'-deoxyguanosine in testes DNA (4.2 +/- 0.2 residue/10(5) dG). The present data suggest that this model of chronic iron overload produced a mild oxidative damage in rat testes that was partially prevented by alphaT supplementation.

Animals↗

PubMed1999

Higher levels of antioxidant defenses in enalapril-treated versus non-enalapril-treated hemodialysis patients.

We previously reported chronic treatment with angiotensin-converting enzyme inhibitors (ACEis) increases antioxidant defenses in mice. In the present study, however, we examined various antioxidant defenses in chronic hemodialysis (HD) patients either treated with enalapril (10 mg/d) for at least 6 months (+ACEi; n = 11) or untreated (-ACEi; n = 11). The relationship between antioxidant status and HD was investigated by determining oxidative stress markers and antioxidant defenses in a group of chronic HD patients (n = 33) and a group of age-matched controls (n = 29). The effect of a single HD session on those parameters was also evaluated. Before an HD session (pre-HD), HD patients had significantly lower levels of red blood cell (RBC) glutathione (GSH), selenium-dependent glutathione peroxidase activity (RBC-Se-GPx), plasma ubiquinol-10, and alpha-tocopherol than controls. In a randomly selected group of patients (n = 19), a single HD session caused an additional decrease in RBC-GSH and plasma ubiquinol-10 levels. Plasma thiobarbituric acid reactive substance (TBARS) levels were significantly greater in pre-HD patients than controls. Post-HD plasma TBARS levels were similar to control values. The cohort of +ACEi HD patients had greater pre-HD RBC-GSH content, RBC-Se-GPx activity, and plasma beta-carotene concentrations than -ACEi patients (RBC-GSH: +ACEi, 3.1 +/- 0.9 micromol/mL packed RBCs [PRBCs]; -ACEi, 1.2 +/- 0.3 micromol/mL PRBCs [P < 0.05 v +ACEi]; RBC-Se-GPx: +ACEi, 5.8 +/- 0.7 U/mL PRBCs; -ACEi, 4.3 +/- 0.2 U/mL PRBCs [P < 0.05 v +ACEi]; plasma beta-carotene: +ACEi, 0.54 +/- 0.16 micromol/L plasma; -ACEi, 0.19 +/- 0.05 micromol/L plasma [P < 0.05 v +ACEi]). Results show profound alterations in the circulating antioxidant systems of chronic HD patients and that additional oxidative stress occurs during the HD procedure. In addition, in +ACEi HD patients, the levels of several antioxidant defenses are greater than in those in -ACEi HD patients.

Adult↗

PubMed1999

Tissue damage in acute myocardial infarction: selective protection by vitamin E.

A growing amount of scientific evidence supports the participation of oxygen radicals in heart disease and, consequently, a protective effect of vitamin E (VE), beta-carotene (BC), and other antioxidants. The aim of this study was to correlate plasma VE and BC concentration with the clinical course of the acute myocardial infarction (AMI). We evaluated 120 patients that were admitted at the coronary units within 12 h after the development of AMI symptoms. The AMI was diagnosed by clinical and biochemical criteria and by electrocardiography and echocardiography. Plasma VE and BC concentration was determined by high performance liquid chromatography. The patients were separated according to the plasma concentration of VE (group H, VE > 17.5 microM; group L, VE < 17.5 microM). Clinical history of patients, age, sex, associated cardiovascular risk factors, AMI localization, hemodynamic class, and the treatment received were similar between different groups. The blood levels of creatine phosphokinase (CK) evaluated either 24- or 48-h after admittance, were higher in group L than in group H (24 h: H = 436 +/- 31 U/ml vs. L = 642 +/- 84 U/ml; p < .005; 48 h: H = 242 +/- 21 U/ml; L = 423 +/- 82 U/ml, p < 0.005). The number of deflexions in the electrocardiogram at admittance (ECG-D) was significantly higher in group L than in group H (4.7 +/- 0.3 vs. 3.7 +/- 0.2; p < .005). The number of new Q waves in the ECG of release (ECG-Q) was higher in group L than in group H (2.9 +/- 0.3 vs. 2.2 +/- 0.2; p < .05). The number of segments affected in the echocardiograms (EC-S) was: L = 5.3 +/- 0.6 vs. H = 4.4 +/- 0.2; p = 0.11. No significant differences in CK levels, ECG-D, ECG-Q, and EC-S were observed when the patients were separated according their plasma BC levels. These results indicate that a high concentration of plasma VE, but not BC, was associated with a diminution in the creatine phosphokinase release and with the AMI extension.

Antioxidants↗

PubMed1998

(+)-Catechin prevents human plasma oxidation.

Based on the recognized capacity of (+)-catechin (CTCH) to prevent free radical-mediated damage in different biological systems, its role in the protection of human plasma from oxidation was investigated. Samples of human blood plasma were incubated with 50 mM AAPH [2,2'-azobis-(2-amidinopropane) clorhidrate] or AMVN [2,2'-azobis(2,4-valeronitrile)], in the absence or the presence of CTCH (0.01 to 1 mM). Lipid oxidation was evaluated measuring the formation of 2-thiobarbituric acid reactive substances (TBARS). Alpha-tocopherol (AT), beta-carotene (BC), and CTCH were measured by reverse phase HPLC with electrochemical detection. TBARS formation was dependent on incubation time and on the nature of the azocompound, yielding 4.8 +/- 0.9, and 14.9 +/- 3.4 microM MDA, after 4 h, in AAPH and AMVN-exposed plasma, respectively. Plasma AT and BC were extensively depleted under these oxidant conditions. The addition of CTCH prevented or delayed the formation of TBARS, and the depletion of AT and BC in a dose dependent manner. This antioxidant effect was dependent on the concentration of CTCH and on the physical characteristics of the radical initiator. CTCH supplementation modified not only the lag time for the antioxidants depletion, but also the consumption rate. These results indicate that CTCH was an effective antioxidant in human blood plasma, delaying the consumption of endogenous lipid soluble antioxidants (AT and BC) and inhibiting lipid oxidation.

Amidines↗

PubMed1997

Evaluation of antioxidants, protein, and lipid oxidation products in blood from sporadic amyotrophic lateral sclerosis patients.

Several parameters indicators of oxidative stress were evaluated in blood from individuals with the sporadic form of amyotrophic lateral sclerosis (SALS) and compared to healthy controls. Plasma levels of 2-thiobarbituric-reactive substances (TBARS), products of lipid peroxidation, were significantly higher (p < 0.03) in the SALS patients compared to controls. The concentration of plasma antioxidants (alpha-tocopherol, beta-carotene, ubiquinol-10 and glutathione) and the activity of red blood cell CuZn superoxide dismutase were not significantly different between the groups. The ratio TBARS/alpha-tocopherol was 47% higher in the SALS individuals than in controls. Protein thiols and protein-associated carbonyls in red blood cell membranes and supernates were similar for both groups. A positive correlation (r2 = 0.91) was found between the concentration of protein-associated carbonyls in red blood cells and the onset of clinical symptoms. These findings are in agreement with several reports showing higher levels of oxidative damage to cell components in ALS.

Adult↗

PubMed1997

Enalapril and captopril enhance antioxidant defenses in mouse tissues.

This study was conducted to investigate a possible systemic effect of angiotensin-converting enzyme inhibitors (ACEi) on tissue antioxidant defenses. CF1 mice (4-mo-old females) were administered either water (control) or water containing enalapril (20 mg/l) or captopril (50 mg/l) during 11 wk. Neither enalapril nor captopril treatment had an effect on body mass or brain, kidney, or heart weight relative to controls. CuZn-superoxide dismutase (SOD) activity was increased by enalapril treatment in kidney medulla (27%), heart (24%), and erythrocytes (19%) and by captopril treatment in kidney medulla (43%) and heart (54%) relative to controls. Mn-SOD and catalase activities were unaffected by either treatment. Enalapril, but not captopril treatment, increased Se-glutathione peroxidase activity in renal medulla (19%). Nonenzymatic antioxidant defenses, evaluated by tert-butyl hydroperoxide-initiated chemiluminescence (HICL), were enhanced in kidney cortex (48%) by enalapril and in brain by enalapril (44%) or captopril (36%) treatment relative to controls. As evaluated in vitro by HICL and thiobarbituric acid-reactive substances formation, captopril had a free radical scavenger activity, whereas neither enalapril nor lisinopril was effective. These results suggest that ACEi may protect tissues from oxidative damage by increasing enzymatic and nonenzymatic antioxidant defenses.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1996

Smoking and low antioxidant levels increase oxidative damage to sperm DNA.

Our previous studies have shown that men with low ascorbate intake have markedly increased oxo8dG in the DNA of their sperm. Because cigarette smoke is high in oxidants and depletes plasma and tissue antioxidants, oxidative DNA damage in sperm and tocopherol and ascorbate levels in seminal plasma were determined in smokers and non-smokers. The level in sperm DNA of oxo8dG, an oxidative lesion of guanine, was 50% higher in smokers compared to nonsmokers (p = 0.005). The concentration of alpha-tocopherol in seminal plasma was decreased in smokers by 32% (p = 0.03). Smoking and low antioxidant levels increase oxidative damage to sperm DNA. We discuss the possibility that paternal smoking causes mutations in sperm that lead to cancer, birth defects, and genetic diseases in offspring.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1996

Oxidant defense systems in testes from zinc-deficient rats.

Previous studies have demonstrated that zinc deficiency can be associated with high rates of oxidative damage to testes lipids, proteins, and DNA in male rats. In the present work, different aspects of the oxidant defense system (enzymes and lipid-soluble antioxidant substances) were characterized in the testes of control and zinc-deficient rats. Seventeen-day-old males were given free access to either a control (25 microg Zn/g) or a zinc-deficient (0.5 microg Zn/g) diet, or the 25 microg Zn/g diet at a level of food intake similar to that of zinc-deficient rats. Animals were sacrificed 14 days after the initiation of the diet. The activities of copper-zinc superoxide dismutase (CuZn SOD) and glutathione reductase (GRed) were significantly higher (34% and 23%, respectively) in testes from the zinc-deficient animals than in those of the ad libitum controls. In testes, the activities of manganese superoxide dismutase (Mn SOD) and glutathione peroxidase (GPx), and the concentration of alpha-tocopherol and ubiquinol-9 and -10 were similar among the groups. However, the ratio of reduced/total concentration of both ubiquinols was higher in the zinc-deficient and restrict-fed animals than in the ad libitum controls. Testes homogenates from the zinc-deficient rats showed a low susceptibility to Fe(II)-induced oxidation, which could be explained in part by a lower peroxidation index, mainly due to the decreased testicular content of the fatty acid 20:4 observed in these animals. In summary, both undernutrition and zinc-deficiency can cause an oxidative stress situation in testes, for which cells tend to compensate by increasing select components of the oxidant defense system.

Animals↗

PubMed1995

Superoxide dismutase and glutathione peroxidase activities are increased by enalapril and captopril in mouse liver.

We have characterized the effect of angiotensin converting enzyme (ACE) inhibitors on the activity of CuZn-superoxide dismutase (CuZn-SOD), Mn-superoxide dismutase (Mn-SOD), catalase, and selenium-dependent glutathione peroxidase (Se-GPx). CF1 mice (4-month-old females) were administered water containing enalapril (20 mg/l) or captopril (50 mg/l), during 4 to 11 weeks. After 11 weeks, enalapril treatment caused an increase in the activity of CuZn-SOD, Mn-SOD and Se-GPx, from 19 +/- 4 to 46 +/- 7, 2.1 +/- 0.2 to 3.8 +/- 0.2 units/mg protein and 27 +/- 3 to 54 +/- 3 milliunits/mg protein, respectively. After 11 weeks, captopril treatment increased the activities (P < 0.05) of CuZn-SOD, MnSOD and Se-GPx to 35 +/- 4, 2.9 +/- 0.2 units/mg protein, and 38 +/- 2 milliunits/mg protein, respectively. Catalase activity was not affected by the treatments. These results suggest that ACE inhibitors may protect cell components from oxidative damage by increasing the enzymatic antioxidant defenses.

Animals↗

PubMed1995

Oxidative damage to lipids and DNA concurrent with decrease of antioxidants in rat testes after acute iron intoxication.

The effect of acute iron overload was studied in rat testes 20 h after a single administration of iron-dextran (500 mg/kg body wt, ip). Total testes iron content was 6.1-fold higher in iron-treated rats compared to controls. The endogenous level of lipid peroxidation was evaluated as 2-thiobarbituric acid-reactive substances (TBARS). Testes iron concentration (0.12-2.67 mumol/g of tissue) was positively correlated (r = 0.86; P < 0.01) with testes TBARS (26.2-77.5 nmol/g tissue). Testes content of lipid-soluble antioxidants, alpha-tocopherol, ubiquinol-9, and ubiquinol-10, were inversely correlated with testes iron content. The steady-state level of 8-oxo-7,8-dihydro-2'-deoxyguanosine in testes DNA was 25% higher (P < 0.01) in iron-treated rats compared to controls (2.4 +/- 0.2 oxo8dG/10(5)dG). The content of protein carbonyl groups (1.45 +/- 0.13 nmol/mg protein) and the activity of glutamine synthase (1.32 +/- 0.07 units/mg protein) were similar for the iron-treated and control rats. Fe treatment did not affect superoxide dismutase, catalase, and glutathione peroxidase activities. The results indicate that acute iron overload causes iron accumulation in rat testes, which is associated with increased lipid and DNA oxidative damage and depletion of lipid-soluble antioxidants.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1995

Zinc deficiency causes oxidative damage to proteins, lipids and DNA in rat testes.

To investigate the effects of zinc deficiency on oxidative damage to testes proteins, lipids and DNA, weanling male rats were allowed free access to low (0.5 microgram Zn/g) or adequate (25 micrograms Zn/g) zinc diets for 14 d. A third group was restricted intake of the adequate Zn diet to the amount consumed by the low Zn diet-fed group. Compared with ad libitum-fed controls, testes from rats fed the low zinc diet had lower glutamine synthetase activity, lower Fe(2+)-stimulated 2-thiobarbituric acid-reactive substances (TBARS) production, higher protein carbonyl concentrations (P < 0.05), and higher 8-oxo-2'-deoxyguanosine levels (P = 0.06). Glutamine synthetase activity in testes of the food-restricted controls was between the values for the ad libitum controls and zinc-deficient animals. Protein carbonyls were higher in the restricted controls compared with the ad libitum controls, whereas stimulated TBARS production was lower (P < 0.05). Levels of 8-oxo-2'-deoxyguanosine were lower in testes DNA of the restricted controls than in the zinc-deficient group (P < 0.05). Testes iron concentrations were higher in the zinc-deficient and restricted control rats than in ad libitum controls (P < 0.05). The oxidative damage observed may have occurred as a consequence of increased reactive oxygen species generation secondary to tissue iron accumulation and/or reductions in zinc-dependent antioxidant processes.

Animals↗

PubMed1994

5-Aminolevulinic acid mediates the in vivo and in vitro formation of 8-hydroxy-2'-deoxyguanosine in DNA.

5-Aminolevulinic acid (ALA), a heme precursor accumulated in chemical and inborn porphyrias, may behave as an endogenous pro-oxidant. In chronically treated rats (40 mg ALA/kg body wt every 2 days for 15 days) the steady-state level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in liver DNA (94.5 +/- 23.3 residues/10(6) dG) was 4.5 times higher than in non-treated rats (21 +/- 7.5 residues/10(6) dG). In vitro exposure of calf thymus DNA to ALA (0.05-5 mM) in the presence of 10 microM Fe2+ caused the formation of 8-OHdG. The amount of 8-OHdG rose from 135 +/- 15 residues/10(6) dG in the control system to 1140 +/- 150 residues/10(6) dG after incubation with 5 mM ALA and 10 microM Fe2+. Diethylenetriaminepentaacetic acid (5 mM) or mannitol (100 mM) inhibited the formation of 8-OHdG by 63 and 69% respectively, evidencing the involvement of both H2O2 and HO. in this process. Hydrogen peroxide (100 microM) or Fe2+ alone did not cause DNA oxidation. The present data support the hypothesis that ALA-generated reactive oxygen species can oxidize DNA and may be involved in the development of primary liver cell carcinoma in individuals with symptomatic acute intermittent porphyria.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1993

Aluminum has both oxidant and antioxidant effects in mouse brain membranes.

The in vitro effects of aluminum (Al) on lipid peroxidation were studied in mouse brain homogenates and purified brain subcellular fractions. In brain homogenates prepared in 5 mM Na2HPO4, 0.14 M NaCl, pH 7.4, the addition of Al decreased Fe(2+)-induced lipid peroxidation, measured as 2-thiobarbituric acid-reactive substances (TBARS), in a dose dependent manner, with a maximum effect at 250 microM Al. In brain homogenates prepared in 20 mM Tris-HCl, 0.14 M NaCl, pH 7.4, Al acted as a prooxidant at 250 and 500 microM concentrations. The prooxidant effect of Al was enhanced with increasing concentrations of Fe2+. In brain microsomes Al increased TBARS production and conjugated dienes formation, both depending on the addition of Fe2+. In myelin, the prooxidant effect of Al on Fe(2+)-induced lipid peroxidation was eliminated when membranes were disrupted with 0.2% Triton X-100. Thus, in brain homogenates, microsomes, and myelin, Al has the potential for exhibiting both prooxidant and antioxidant activity depending on the concentration of Fe2+ and Al in the media and on membrane integrity. Similar to Al, Be2+ and La3+ had prooxidant effects on Fe(2+)-induced lipid peroxidation in myelin, suggesting that membrane damage secondary to induced lipid peroxidation may be a common mechanism underlying tissue pathology even with metals without redox capacity. Oxidative damage to brain cell components may be an important mechanism mediating the neurotoxicity of Al.

Aluminum↗

PubMed1991

Ascorbic acid protects against endogenous oxidative DNA damage in human sperm.

Damage to the DNA of germ cells can lead to mutation, which may result in birth defects, genetic diseases, and cancer. The very high endogenous rate of oxidative DNA damage and the importance of dietary ascorbic acid (AA) in preventing this damage has prompted an examination of these factors in human sperm DNA. The oxidized nucleoside 8-hydroxy-2'-deoxyguanosine (8-oxo-7,8-dihydro-2'-deoxyguanosine; oxo8dG), 1 of approximately 20 major products of oxidative damage to DNA, was measured in DNA isolated from human sperm provided by healthy subjects and compared to the seminal fluid AA levels. This relationship was studied in two groups. In a group of 24 free-living individuals 20-50 years old high levels of oxo8dG were correlated with low seminal plasma AA. The endogenous level of oxo8dG in this group was 13 fmol per microgram of DNA or approximately 25,000 adducts per sperm cell. The second group of individuals was maintained on a controlled diet that varied only in AA content. When dietary AA was decreased from 250 to 5 mg/day, the seminal fluid AA decreased by half and the level of oxo8dG in sperm DNA increased 91%. Repletion of dietary AA for 28 days (from 5 mg/day to 250 or 60 mg/day) caused a doubling in seminal fluid AA and reduced oxo8dG by 36%. These results indicate that dietary AA protects human sperm from endogenous oxidative DNA damage that could affect sperm quality and increase risk of genetic defects, particularly in populations with low AA such as smokers.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1991

Immunocompetence and oxidant defense during ascorbate depletion of healthy men.

To determine nonscorbutic effects of moderate vitamin C deficiency we measured immune function and oxidative damage in eight healthy men (25-43 y) who consumed 5-250 mg/d of ascorbic acid over 92 d on a metabolic unit. During ascorbic acid intakes of 5, 10, or 20 mg/d, subjects attained a state of moderate ascorbic acid deficiency as ascorbic acid concentrations in plasma, leucocytes, semen, and buccal cells dropped to less than 50% of baseline with no scorbutic symptoms observed. No changes in cell proliferation, erythrocyte antioxidant enzymes, and DNA strand breaks were observed; however, blood levels of glutathione and NAD(P) decreased during ascorbic acid deficiency, as did delayed hypersensitivity responsiveness. Concentrations of the oxidatively modified DNA base, 8-hydroxydeoxyguanosine in sperm DNA and fecapentaenes, ubiquitous fecal mutagens, were increased during ascorbic acid depletion. Moderate vitamin C deficiency, in the absence of scurvy, results in alteration of antioxidant chemistries and may permit increased oxidative damage.

Adult↗

PubMed1990

Lability of red blood cell membranes to lipid peroxidation: application to humans fed polyunsaturated lipids.

Red blood cell membranes (RBCM) were used to estimate human red blood cell lability to lipid peroxidation in vitro. RBCM were prepared from blood collected from humans fed diets with either 3 or 15% polyunsaturated fatty acids for 80 days. RBCM were isolated by centrifugation, and oxidative stress was induced by in vitro incubation with 0.1 or 0.5 mM tert-butyl hydroperoxide (t-BOOH) in the presence of 0.5 mg added hemoglobin. Lipid Peroxidation was evaluated by measurement of thiobarbituric acid-reactive substances (TBARS). Lipid peroxidation correlated with the protein content of RBCM in both noninduced and t-BOOH-induced lipid peroxidation systems. TBARS production was dependent on the amount of t-BOOH added to the RBCM. The production of TBARS by RBCM incubated with 0.5 mM t-BOOH was correlated with arachidonic acid content in the red blood cells (RBC) from which RBCM were prepared. The methodology developed was useful for comparative estimations of the lability of RBCM to lipid peroxidation.

Adult↗

PubMed1990

Effects of aluminum on brain lipid peroxidation.

Excessive dietary aluminum (Al) has been proposed to be a factor contributing to several neurological disorders in humans. Six 8-week-old female Swiss Webster mice were fed for 10 weeks purified diets containing 100 (control, 100 Al), 500 (500 Al) or 1000 (1000 Al) micrograms Al/g diet. Brain and liver lipid peroxidation was determined by evaluating the production of 2-thiobarbituric acid reactive substances (TBARS) in brain and liver homogenates in the presence or absence of 50 microM ferrous iron. TBARS production in the absence of iron in brain homogenates from mice fed the 1000 Al diet was higher (30%) than that in the 100 Al control group (3.1 vs. 2.4 nmol TBARS/mg protein). The addition of ferrous iron increased TBARS production in brain homogenates from all 3 dietary groups. The iron-induced TBARS production was 26% higher in the 1000 Al brain homogenates than in the 100 Al group (4.9 vs. 3.9 nmol TBARS/mg protein). Brain TBARS production in the presence and absence of iron was similar between the 100 and 500 Al groups. TBARS production in liver homogenates measured either with or without iron was similar for the 3 groups. These results show that, in mice, dietary Al intoxication leads to increased brain TBARS production, suggesting that enhanced lipid peroxidation may be one possible mechanism underlying the neurological damage associated with increased tissue Al.

Aluminum↗

PubMed1990

Oxidative damage to DNA during aging: 8-hydroxy-2'-deoxyguanosine in rat organ DNA and urine.

Oxidative damage to DNA is shown to be extensive and could be a major cause of the physiological changes associated with aging and the degenerative diseases related to aging such as cancer. The oxidized nucleoside, 8-hydroxy-2'-deoxyguanosine (oh8dG), one of the approximately 20 known oxidative DNA damage products, has been measured in DNA isolated from various organs of Fischer 344 rats of different ages. oh8dG was present in the DNA isolated from all the organs studied: liver, brain, kidney, intestine, and testes. Steady-state levels of oh8dG ranged from 8 to 73 residues per 10(6) deoxyguanosine residues or 0.2-2.0 x 10(5) residues per cell. Levels of oh8dG in DNA increased with age in liver, kidney, and intestine but remained unchanged in brain and testes. The urinary excretion of oh8dG, which presumably reflects its repair from DNA by nuclease activity, decreased with age from 481 to 165 pmol per kg of body weight per day for urine obtained from 2-month- and 25-month-old rats, respectively. 8-Hydroxyguanine, the proposed repair product of a glycosylase activity, was also assayed in the urine. We estimate approximately 9 x 10(4) oxidative hits to DNA per cell per day in the rat. The results suggest that the age-dependent accumulation of oh8dG residues observed in DNA from liver, kidney, and intestine is principally due to the slow loss of DNA nuclease activity; however, an increase in the rate of oxidative DNA damage cannot be ruled out.

8-Hydroxy-2'-Deoxyguanosine↗